Kenji Yoshiyama

The effect of musical experience on hemispheric lateralization in musical feature processing

Music consists of a variety of spectral and temporal features. Generally, brain processing of these features is reported as being right hemisphere dominant. However, there are contradicting results as to whether musical experience affects hemispheric laterality or not. In the present study, we investigated the effect of musical experience on hemispheric lateralization of musical feature processing using magnetoencephalography (MEG). Mismatch fields (MMFs) were measured from 8 musicians and 8 nonmusicians in oddball tasks with four different musical features, including pitch, chord, timbre and rhythm. Regardless of the features, the MMFs showed right-hemispheric dominance in nonmusicians, whereas musicians showed symmetrical MMF amplitudes in both hemispheres. The electrical activity around the auditory cortex to the MMFs also supported the right-hemispheric dominance in nonmusicians and bilateral activation in musicians. Voxel-based morphometry did not detect any group differences around the auditory cortices. These results suggest that musical training changes the hemispheric roles for musical feature processing in the pre-attentive stage, and this functional alteration can occur without apparent anatomical changes.

Classification of delusions in Alzheimer's disease and their neural correlates

Background:  Previous findings on neural correlates of delusion in Alzheimers disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data.

Functional connectivity assessed by resting state EEG correlates with cognitive decline of Alzheimer’s disease – An eLORETA study

OBJECTIVE To explore neurophysiological biomarkers of Alzheimers disease (AD), we investigated electroencephalography (EEG) of AD patients, and assessed lagged phase synchronization, a measure of brain functional connectivity. METHODS Twenty-eight probable AD patients and 30 healthy controls (HC) were enrolled. Forty seconds of artifact-free EEG data were selected and compared between patients with AD and HC. Current source density (CSD) and lagged phase synchronization were analyzed by using eLORETA. RESULTS Patients with AD showed significantly decreased lagged phase synchronization between most cortical regions in delta band relative to controls. There also was a decrease in lagged phase synchronization between the right dorsolateral prefrontal cortex (DLPFC) and the right posterior-inferior parietal lobule (pIPL) in theta band. In addition, some connections in delta band were found to be associated with cognitive function, measured by MMSE. This involved specifically interhemispheric temporal connections as well as left inferior parietal connectivity with the left hippocampus, lateral frontal regions, and the anterior cingulate cortex (aCC). Right temporal connections in delta band were related to global function, as estimated by CDR. No differences were found in CSD analysis between patients and HC. CONCLUSIONS Functional connectivity disruptions between certain brain regions, as measured with lagged phase synchronization, may potentially represent a neurophysiological biomarker of AD. SIGNIFICANCE Our study indicated that AD and healthy elderly could have the different patterns of lagged phase synchronization.

Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias

Background/Aims Behavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD). Methods We gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR). Results Significant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD. Conclusions As dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear.

The Neural Basis of Perceptual and Conceptual Word Priming – a Pet Study

Positron emission tomography scans were obtained in 13 normal subjects during perceptual and conceptual word priming tasks with the aim to investigate the neural system specific to the two priming conditions. In the prescan phase, subjects were primed perceptually or conceptually with two separate procedures, while in the scan phase, they performed the same stem completion task. Therefore we could compare the results of the two priming tasks in a direct manner. A fixation control task and a baseline task (completion of stems that did not correspond to previously seen words) were also given. A specific blood flow decrease was found in the left inferior temporal cortex in the perceptual word priming condition and in the left superior temporal / inferior parietal cortex in the conceptual word priming condition. Each blood flow change may reflect transient changes in the cortical areas subserving the processing of the perceptual and conceptual components of word priming.

Sleep disturbances are key symptoms of very early stage Alzheimer disease with behavioral and psychological symptoms: a Japan multi‐center cross‐sectional study (J‐BIRD)

Sleep disturbances in Alzheimer disease (AD) may affect behavioral and psychological symptoms of dementia (BPSD). Our aim was to elucidate the associations between sleep disturbances and other BPSD at different stages of AD.

Association between Milder Brain Deformation before a Shunt Operation and Improvement in Cognition and Gait in Idiopathic Normal Pressure Hydrocephalus

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.

Clinical psychological tests useful for differentiating depressive state with Alzheimer's disease from major depression of the elderly

Background:  A depressive state with Alzheimers disease (AD) is difficult to differentiate from major depression (MD) in many cases. The purpose of this study was to identify differences between the two disorders using a battery of clinically available psychological tests.

Architecture of binocular disparity processing in monkey inferior temporal cortex.

Neurons in the inferior temporal (IT) cortex respond not only to the shape, color or texture of objects, but to the horizontal positional disparity of visual features in the right and left retinal images. IT neurons with similar shape selectivity cluster in columns. In this study, we examined how IT neurons are spatially arranged in the IT according to their selectivity for binocular disparity. With a single electrode, we simultaneously recorded extracellular action potentials from a single neuron and those from background multiple neurons at the same sites or recorded multineuronal responses at successive sites along electrode penetrations, while monkeys performed a fixation task. For neurons at each recording site, effective shapes were first determined from a set of 20 shapes presented at the zero-disparity plane. The most effective shape was then presented with varying amounts of disparity. Single neuron responses and background multiunit responses recorded at the same sites showed a similar ability of disparity discrimination and tended to share the preferred disparity, suggesting that neurons with similar disparity selectivity are clustered in the IT. We estimated from sequential recordings along electrode penetrations that the size of the neuronal clusters with similar disparity selectivity was smaller than the size of clusters with similar shape selectivity.

EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or “CSF tapping” is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified “shunt responders” and “shunt nonresponders” with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.